Adherence to oral anticoagulant treatment and risk factor assessment six months after DC-conversion of atrial fibrillation.

Objective. We wanted to study the adherence of oral anticoagulant treatment in patients 6 months after elective DC-cardioversion and to observe possible increases in CHA2DS2-VASc scores and new adverse outcomes. Design. Consecutive patients admitted for elective DC-cardioversion at Haukeland University Hospital during the period from June 2017 to April 2018 were screened. Only patients who had a DC-cardioversion performed were included. Baseline information was collected from hospital records and follow up information was gathered through a structured phone interview and the prescription database. Results. Of the 125 patients screened, 38 were excluded as DC-cardioversion was not performed. The included patients were contacted 6 months later, out of whom 77 (84%) responded. Three patients had discontinued oral anticoagulation therapy, but only one patient had done so in violation of Guidelines. Two patients had continued oral anticoagulant treatment despite lack of indication. Of the responding patients 89% were compliant, estimated by a Proportion of Days Covered > 80%. Three patients experienced a thromboembolic event, despite being on anticoagulation. The mean CHA2DS2-VASc score increased from 3.0 ± 1.4 to 3.3 ± 1.5, (p < .001). Less than half maintained sinus rhythm, the remaining had either atrial fibrillation (n = 30, 40%) or were unsure of their current rhythm (n = 9, 12%). A third received new cardiac interventions during follow up. Conclusion. We found an excellent adherence to Guidelines recommended therapy amongst our patients. CHA2DS2-VASc scores increased significantly during the 6-month observation period. From this we conclude there is a need for structured follow up to assess new risk factors.

Static patella tilt and axial engagement in knee extension are mainly influenced by knee torsion, the tibial tubercle-trochlear groove distance (TTTG), and trochlear dysplasia but not by femoral or tibial torsion.

PURPOSE: The aim of this study was to investigate the association of femoral (FT), tibial (TT), and knee torsion (KT) on the patella tilt (PT), the axial engagement index (AEI), and the tibial tuberosity-trochlear groove distance (TTTG). METHODS: Femoral torsion, tibial torsion, knee torsion, patella tilt, the axial engagement index, the TTTG, and trochlear dysplasia were retrospectively evaluated on 59 patients suffering from recurrent patella instability or anterior knee pain with 118 torsional lower limb magnetic resonance imaging studies. RESULTS: FT and TT did not show any significant associations with TTTG, PT, and AEI (n.s.). KT was significantly associated with a higher TTTG, higher PT, and lower AEI (all, p < 0.001). Higher grade trochlear dysplasia was associated with a higher PT and lower AEI (both, p < 0.001). The Dejour classification showed no significant association with FT, TT, KT, and TTTG (n.s.). All measurement parameters showed an excellent interrater agreement (ICC 0.89-0.97). CONCLUSIONS: Static patella tilt and patellofemoral axial engagement in knee extension are mainly influenced by knee torsion, TTTG, and trochlear dysplasia but not by femoral or tibial torsion. These findings help to understand the underlying reasons for the patella position in knee extensions in CT and MRI investigations in patients suffering from patella instability and patellofemoral pain syndrome. LEVEL OF EVIDENCE: III.

Searching for light dark matter with the SLAC millicharge experiment.

New sub-GeV gauge forces ("dark photons") that kinetically mix with the photon provide a promising scenario for MeV-GeV dark matter and are the subject of a program of searches at fixed-target and collider facilities around the world. In such models, dark photons produced in collisions may decay invisibly into dark-matter states, thereby evading current searches. We reexamine results of the SLAC mQ electron beam dump experiment designed to search for millicharged particles and find that it was strongly sensitive to any secondary beam of dark matter produced by electron-nucleus collisions in the target. The constraints are competitive for dark photon masses in the ~1-30 MeV range, covering part of the parameter space that can reconcile the apparent (g-2)(µ) anomaly. Simple adjustments to the original SLAC search for millicharges may extend sensitivity to cover a sizable portion of the remaining (g-2)(µ) anomaly-motivated region. The mQ sensitivity is therefore complementary to ongoing searches for visible decays of dark photons. Compared to existing direct-detection searches, mQ sensitivity to electron-dark-matter scattering cross sections is more than an order of magnitude better for a significant range of masses and couplings in simple models.

Efficacy of a Mouthwash Containing CHX and CPC in SARS-CoV-2-Positive Patients: A Randomized Controlled Clinical Trial.

Soon after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, preprocedural mouthwashes were recommended for temporarily reducing intraoral viral load and infectivity of individuals potentially infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to protect medical personnel. Particularly, the antiseptic cetylpyridinium chloride (CPC) has shown virucidal effects against SARS-CoV-2 in vitro. Therefore, the aim of this randomized controlled clinical trial was to investigate the efficacy of a commercially available mouthwash containing CPC and chlorhexidine digluconate (CHX) at 0.05% each in SARS-CoV-2-positive patients as compared to a placebo mouthwash. Sixty-one patients who tested positive for SARS-CoV-2 with onset of symptoms within the last 72 h were included in this study. Oropharyngeal specimens were taken at baseline, whereupon patients had to gargle mouth and throat with 20 mL test or placebo (0.9% NaCl) mouthwash for 60 s. After 30 min, further oropharyngeal specimens were collected. Viral load was analyzed by quantitative reverse transcriptase polymerase chain reaction, and infectivity of oropharyngeal specimens was analyzed by virus rescue in cell culture and quantified via determination of tissue culture infectious doses 50% (TCID50). Data were analyzed nonparametrically (α = 0.05). Viral load slightly but significantly decreased upon gargling in the test group (P = 0.0435) but not in the placebo group. Viral infectivity as measured by TCID50 also significantly decreased in the test group (P = 0.0313), whereas there was no significant effect but a trend in the placebo group. Furthermore, it was found that the specimens from patients with a vaccine booster exhibited significantly lower infectivity at baseline as compared to those without vaccine booster (P = 0.0231). This study indicates that a preprocedural mouthwash containing CPC and CHX could slightly but significantly reduce the viral load and infectivity in SARS-CoV-2-positive patients. Further studies are needed to corroborate these results and investigate whether the observed reductions in viral load and infectivity could translate into clinically useful effects in reducing COVID-19 transmission (German Clinical Trials Register DRKS00027812).

Durable memories and efficient neural coding through mnemonic training using the method of loci.

Mnemonic techniques, such as the method of loci, can powerfully boost memory. We compared memory athletes ranked among the world's top 50 in memory sports to mnemonics-naïve controls. In a second study, participants completed a 6-week memory training, working memory training, or no intervention. Behaviorally, memory training enhanced durable, longer-lasting memories. Functional magnetic resonance imaging during encoding and recognition revealed task-based activation decreases in lateral prefrontal, as well as in parahippocampal and retrosplenial cortices in both memory athletes and participants after memory training, partly associated with better performance after 4 months. This was complemented by hippocampal-neocortical coupling during consolidation, which was stronger the more durable memories participants formed. Our findings advance knowledge on how mnemonic training boosts durable memory formation through decreased task-based activation and increased consolidation thereafter. This is in line with conceptual accounts of neural efficiency and highlights a complex interplay of neural processes critical for extraordinary memory.

Continuity in evolution: on the nature of transitions.

To distinguish continuous from discontinuous evolutionary change, a relation of nearness between phenotypes is needed. Such a relation is based on the probability of one phenotype being accessible from another through changes in the genotype. This nearness relation is exemplified by calculating the shape neighborhood of a transfer RNA secondary structure and provides a characterization of discontinuous shape transformations in RNA. The simulation of replicating and mutating RNA populations under selection shows that sudden adaptive progress coincides mostly, but not always, with discontinuous shape transformations. The nature of these transformations illuminates the key role of neutral genetic drift in their realization.

Galileo at Io: results from high-resolution imaging.

During late 1999/early 2000, the solid state imaging experiment on the Galileo spacecraft returned more than 100 high-resolution (5 to 500 meters per pixel) images of volcanically active Io. We observed an active lava lake, an active curtain of lava, active lava flows, calderas, mountains, plateaus, and plains. Several of the sulfur dioxide-rich plumes are erupting from distal flows, rather than from the source of silicate lava (caldera or fissure, often with red pyroclastic deposits). Most of the active flows in equatorial regions are being emplaced slowly beneath insulated crust, but rapidly emplaced channelized flows are also found at all latitudes. There is no evidence for high-viscosity lava, but some bright flows may consist of sulfur rather than mafic silicates. The mountains, plateaus, and calderas are strongly influenced by tectonics and gravitational collapse. Sapping channels and scarps suggest that many portions of the upper approximately 1 kilometer are rich in volatiles.

Structural parameters affecting the kinetics of RNA hairpin formation.

There is little experimental knowledge on the sequence dependent rate of hairpin formation in RNA. We have therefore designed RNA sequences that can fold into either of two mutually exclusive hairpins and have determined the ratio of folding of the two conformations, using structure probing. This folding ratio reflects their respective folding rates. Changing one of the two loop sequences from a purine- to a pyrimidine-rich loop did increase its folding rate, which corresponds well with similar observations in DNA hairpins. However, neither changing one of the loops from a regular non-GNRA tetra-loop into a stable GNRA tetra-loop, nor increasing the loop size from 4 to 6 nt did affect the folding rate. The folding kinetics of these RNAs have also been simulated with the program 'Kinfold'. These simulations were in agreement with the experimental results if the additional stabilization energies for stable tetra-loops were not taken into account. Despite the high stability of the stable tetra-loops, they apparently do not affect folding kinetics of these RNA hairpins. These results show that it is possible to experimentally determine relative folding rates of hairpins and to use these data to improve the computer-assisted simulation of the folding kinetics of stem-loop structures.

RNA structures and folding: from conventional to new issues in structure predictions.

Prediction and modeling of RNA structures has become an indispensable tool of biological research disciplines. Currently, reliable predictions require massive input of experimental data. Structure-forming elements are conventional base pairs, as well as a rapidly increasing repertoire of novel structural motifs. New developments extend structural analysis beyond the one-sequence/one-structure paradigm and allow questions that are relevant to molecular evolution to be answered.

[Reconstruction of the medial patellofemoral ligament using autologous gracilis tendon in an implant-free technique on the patellar side]. / Rekonstruktion des medialen patellofemoralen Ligaments mit autologer Grazilissehne in patellarseitig implantatfreier Technik.

OBJECTIVE: Anatomic reconstruction of the medial patellofemoral ligament using autologous gracilis tendon in an implant-free technique on the patellar side to regain patellofemoral stability. INDICATIONS: Recurrent dislocations, primary dislocation with high risk of recurrence, and dislocations with (osteo-)chondral flake fractures. As combined approach together with other procedures (trochleoplasty, tibial tubercle osteotomy). Revisions. CONTRAINDICATIONS: As an isolated procedure in patients with high degrees of trochlear dysplasia, chronic dislocation of the patella, and patellofemoral maltracking without instability. SURGICAL TECHNIQUE: Harvesting of the gracilis tendon. Drilling of a V-shaped tunnel with a special aiming device in anatomic position on the medial side of the patella. Drilling of a femoral tunnel in anatomic position under fluoroscopic control. Passage of the graft, arthroscopic-guided tensioning, and femoral fixation with a biodegradable interference screw. POSTOPERATIVE MANAGEMENT: Partial weight bearing (20 kg) for 1-2 weeks. No limitation in range of motion. No orthosis. Specific sports allowed after approximately 3 months. RESULTS: Perioperative complications associated specifically with the technique were observed in 1.0% (7 of 729 cases). In a series of 72 consecutive cases from May 2010 to October 2010, the following were recorded after 4.0 ± 0.1 years: recurrent dislocations in 3.2%, a Tegner activity score of 5.1 ± 1.8, and subjective satisfaction in 92% (follow-up rate 87.5%). No fracture of the patella was seen in any of our patients.

Laparotomy closure using an elastic suture: a promising approach.

BACKGROUND: Midline laparotomy wound failure like burst abdomen remains one of the major complications after abdominal surgery. The use of sutures with a closer resemblance to abdominal wall physiology, like elastic threads, could decrease the risk of these complications occurring. Thus, we evaluated the possibility of using a new elastic thread composed of thermoplastic polyurethane (TPU) as a suture for the closure of midline laparotomies compared to conventionally used polypropylene (PP) in a rabbit model. METHODS: The elastic TPU thread was processed and tensile tests were performed. Twenty female chinchilla rabbits underwent midline laparotomy. They were randomized to a TPU and a PP group depending on the suture used for fascia closure. After 7 or 21 days, the abdominal walls were assessed macroscopically for wound healing complications and were explanted for histopathological investigation. RESULTS: Tensile tests showed a mean elastic elongation of 55.5% and a sufficient material strength of the TPU thread. In animal experiments, there was no difference between the groups at 7 days; however, the TPU suture showed significantly less CD68 positive cells (p < 0.001) and a higher collagen I/III ratio (p = 0.011) than PP did after 21 days. The amount of apoptotic cells was significantly elevated in the TPU group (p = 0.007) after 21 days. No differences were found concerning granuloma size and number of Ki67-positive cells. CONCLUSIONS: The newly developed TPU thread shows promising tensile characteristics. Midline laparotomy closure is feasible and safe in a rabbit model. Immunohistochemistry indicates similar biocompatibility and wound healing after implantation compared to PP after 21 days. To confirm these findings and to proof long-term capability further studies need to be conducted.

From sequences to shapes and back: a case study in RNA secondary structures.

RNA folding is viewed here as a map assigning secondary structures to sequences. At fixed chain length the number of sequences far exceeds the number of structures. Frequencies of structures are highly non-uniform and follow a generalized form of Zipf's law: we find relatively few common and many rare ones. By using an algorithm for inverse folding, we show that sequences sharing the same structure are distributed randomly over sequence space. All common structures can be accessed from an arbitrary sequence by a number of mutations much smaller than the chain length. The sequence space is percolated by extensive neutral networks connecting nearest neighbours folding into identical structures. Implications for evolutionary adaptation and for applied molecular evolution are evident: finding a particular structure by mutation and selection is much simpler than expected and, even if catalytic activity should turn out to be sparse of RNA structures, it can hardly be missed by evolutionary processes.

Comorbidity in primary care: presentation and consequences.

Comorbidity is a well-established phenomenon in depressive disorders, and it is widely agreed that the majority of depressive disorders examined in both primary care and the general population are not "pure." This article reviews comorbidity findings in general population and primary care surveys. The implications of comorbid depressive disorders are discussed in terms of their presentation and recognition in primary care, patterns of course and outcome, and associated impairments and disabilities. Data from a World Health Organization study, conducted in primary health clinics in 15 countries, demonstrate that 62% of all depressive cases also suffer from at least one other current mental disorder and that the primary reason for patient visits is rarely of a psychological nature, with the majority of attendees complaining primarily of somatic symptoms (41%), pains (37%), and fatigue and sleep problems (12%). Similar results are presented from 2 recent large representative population surveys, the National Comorbidity Survey and the Early Developmental Stages of Psychopathology Study. The implications of such comorbidity are viewed from various perspectives: the form of depressive presentations in primary care, the recognition of depression in health care, and health services utilization, impairments and disabilities, and course and outcome.

How to search for RNA structures. Theoretical concepts in evolutionary biotechnology.

The relation between RNA sequences and minimum free energy secondary structures is viewed as a mapping from sequence space into shape space. The properties of such mappings depend strongly on the ratios of the numbers of sequences and structures and, hence, substantial differences are observed between samples of structures derived from AUGC, pure AU or pure GC sequences. Statistical analysis of large samples is used to demonstrate that structures from AUGC sequences are much less sensitive to point mutations than those from sequences containing exclusively AU or GC. The frequency with which a structure is realized in sequence space is inversely proportional to some power c > 1 of the structure's frequency rank, thus following a (generalized) Zipf law. For long sequences the exponent approaches c = 1. An inverse folding algorithm is used to compute samples of sequences folding into the same secondary structure. These sequences are distributed randomly in sequence space. Common structures form extended neutral networks along which populations can migrate through the entire sequence space without changing structure. In this migration, moves of Hamming distance d = 1 and d = 2 are accepted in order to allow for base and base pair exchanges, respectively. Around any arbitrarily chosen sequence a ball that contains sequences folding into all common structures can be drawn. This ball has a diameter that is much smaller than the diameter of sequence space. Hence, only a small fraction of sequence space needs to be searched in order to find a given structure. The results derived from the mapping of sequences into structures are used to suggest a rationale for evolutionary searches on RNA structures: selection cycles with high and low mutation rates applied in alternation. Generalizations of the results to RNA 3-D structures and protein structures are discussed.

Patterns of cannabis use, abuse and dependence over time: incidence, progression and stability in a sample of 1228 adolescents.

AIMS: To present data on the incidence of cannabis use at follow-up, and its progression, stability, abuse and dependence in a representative sample of adolescents (N = 1228), aged 14-17 years at "baseline"--the outset of the study--in Munich, Germany. DESIGN: The study employed a prospective longitudinal design using a representative population sample. The mean follow-up time was 19.7 months. The Composite International Diagnostic Interview (M-CIDI) was used to assess patterns of use, abuse and dependence according to DSM-IV criteria. FINDINGS: (1) In our sample, 34.8% of males and 30.2% of females had tried cannabinoids at least once. (2) Of those who used cannabis repeatedly (two or four times) at baseline, 26.1% stopped using by follow-up; the majority went on to regular use in the follow-up period. Similarly, only 17.7% of the regular users at the outset stopped using cannabis completely; 74.2% continued their pattern of regular use. Thus, the higher the baseline use pattern, the higher was the probability of continued or heavier use during follow-up. (3) Although the cumulative life-time incidence for DSM-IV cannabis abuse (3.5%) in this age group was low, it is noteworthy that complete diagnostic remissions were relatively rare (31.7% for dependence, 41.1% for abuse). (4) There was considerable concurrent use of other drugs. CONCLUSIONS: Cannabis use was almost as widespread in this sample of adolescents in Germany as in similar age groups in metropolitan areas of North America. There was a relatively low spontaneous remission rate among regular and repeated users. Cannabis use in adolescence appears to be less transient than many people would believe.

Covariates of cannabis use progression in a representative population sample of adolescents: a prospective examination of vulnerability and risk factors.

UNLABELLED: AIMS/DESIGN: This study reports findings concerning risk factors for first, "repeated" and "regular" use of cannabis in respondents (N = 1228) who were aged 14-17 years at the outset (i.e. at "baseline") as part of a longitudinal prospective community study (EDSP). Risk factors were assessed at baseline or by separate interviews with the respondents' parents. Cumulative life-time cannabis use was the main outcome measure in this study--assessed by information from both the baseline and the follow-up investigation at an average of 19.7 months later. A cumulative logistic regression model was used to estimate associations. FINDINGS: Using seven of a total of 25 variables examined, the final model classified 72.1% of respondents correctly. Family history of substance use disorders, self-esteem and competence, unconditional commitment to not using drugs, immediate availability of drugs, peer group drug use and previous history of nicotine dependence and alcohol use disorders all contributed significantly to the final model, predicting the progression to cannabis use from "no use", to "one time only", "repeated use", and "regular use". CONCLUSION: In addition to well-documented risk factors such as peer group pressure, availability, low self-esteem and competence, findings suggest that family history and prior experiences with legal drugs play a significant role in the early development of cannabis consumption in teenagers.

Genotypes with phenotypes: adventures in an RNA toy world.

Evolution has created the complexity of the animate world and deciphering the language of evolution is the key towards understanding nature. The dynamics of evolution is simplified by considering it as a superposition of three less sophisticated processes: population dynamics, population support dynamics, and genotype-phenotype mapping. Evolution of molecules in laboratory assays provides a sufficiently simple system for the quantitative analysis of the three phenomena. Coarse-grained notions of structures like RNA secondary structures are used as model phenotypes. They provide an excellent tool for a comprehensive analysis of the entire complex of molecular evolution. The mapping from RNA genotypes into secondary structures is highly redundant. In order to find at least one sequence for every common structures one need only search a (relatively) small part of sequence space. The existence of selectively neutral phenotypes plays an important role for the the success and the efficiency of evolutionary optimization. Molecular evolution found a highly promising technological application in the design of biomolecules with predefined properties.

Self-replication with errors. A model for polynucleotide replication.

A model for polynucleotide replication is presented and analyzed by means of perturbation theory. Two basic assumptions allow handling of sequences up to a chain length of v approximately 80 explicitly: point mutations are restricted to a two-digit model and individual sequences are subsumed into mutant classes. Perturbation theory is in excellent agreement with the exact results for long enough sequences (v greater than 20).

A computer model of evolutionary optimization.

Molecular evolution is viewed as a typical combinatorial optimization problem. We analyse a chemical reaction model which considers RNA replication including correct copying and point mutations together with hydrolytic degradation and the dilution flux of a flow reactor. The corresponding stochastic reaction network is implemented on a computer in order to investigate some basic features of evolutionary optimization dynamics. Characteristic features of real molecular systems are mimicked by folding binary sequences into unknotted two-dimensional structures. Selective values are derived from these molecular 'phenotypes' by an evaluation procedure which assigns numerical values to different elements of the secondary structure. The fitness function obtained thereby contains nontrivial long-range interactions which are typical for real systems. The fitness landscape also reveals quite involved and bizarre local topologies which we consider also representative of polynucleotide replication in actually occurring systems. Optimization operates on an ensemble of sequences via mutation and natural selection. The strategy observed in the simulation experiments is fairly general and resembles closely a heuristic widely applied in operations research areas. Despite the relative smallness of the system--we study 2000 molecules of chain length v = 70 in a typical simulation experiment--features typical for the evolution of real populations are observed as there are error thresholds for replication, evolutionary steps and quasistationary sequence distributions. The relative importance of selectively neutral or almost neutral variants is discussed quantitatively. Four characteristic ensemble properties, entropy of the distribution, ensemble correlation, mean Hamming distance and diversity of the population, are computed and checked for their sensitivity in recording major optimization events during the simulation.

The Ohio AIDS Prevention Survey: a study of psychometric properties.

The reliability of a measuring instrument is a major criterion for assessing its quality and adequacy. This article describes reliability pilot testing done with the Ohio AIDS Prevention Survey (Fellner & Thomas, 1989-90) in a sample of sexually active women of childbearing age. Previous alpha reliabilities of the knowledge scale of the survey have ranged from .71-.81, while the reliabilities of the attitudes and beliefs scale have ranged from .33-.45. In this sample, reliability measures for the knowledge and attitudes and beliefs scales were .65 and .45, respectively. The results of this study indicate that the Ohio AIDS Prevention Survey is clearly in its developmental stages and that further development of the survey is necessary prior to continued use in public health settings.